Neurotrophins play an essential role in the production, survival and maintenance of neurons in peripheral nerve ganglia. However, little is known about the impact of neurotrophins on the actual innervation of the skin where the full range of neuronal phenotypes and target selection are expressed. The wide variety of organized sensory and autonomic endings in the mystacial pad will be used in an assay to test several hypotheses about neurotrophin signaling mechanisms. These hypotheses are based on several important and surprising observations about the impact of null mutations and overexpression of neurotrophins in skin. The PI now plans to determine neurotrophin receptor expressions for each of the developing sets of innervation to the normal mouse and rat mystacial pad. Neurotrophin receptor expression will also be studied in mice with null mutations for neurotrophins and their receptors and in transgenic mice overexpressing neurotrophins in the skin. The impact of NGF and NT-3 overexpression on sensory and sympathetic endings will be assessed. Finally, the role of p75 in mediating the dramatic suppression of terminal arborization mediated by BDNF will be assessed. These studies should enhance our understanding of the role of neurotrophins and their receptors in regulating the development of specific types cutaneous innervation.